Northern Blood Research Centre, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia.
Thromb Haemost. 2012 Mar;107(3):575-83. doi: 10.1160/TH11-09-0631. Epub 2012 Jan 11.
Heparin-induced thrombocytopenia (HIT) remains a challenge, with diagnosis confirmed only by functional assays. The gold standard 14C-serotonin release assay (SRA) is highly sensitive but technically challenging and unsuitable for routine use. We conducted a large study to validate whole blood impedance aggregometry (WBIA) as a suitable diagnostic tool for HIT. WBIA and SRA were used to test 181 samples positive for H-PF4 antibodies by PaGIA or ELISA. Using the same high responder donor, 77 samples were positive by WBIA (aggregation with low-dose but not high-dose heparin). Using the strict definition for SRA positivity, 72 samples were true HIT. In nine samples, serotonin release with high-dose heparin dropped by > 50% but was still >20%; these were retested after a one-half dilution and 8/9 became positive. Ten other samples were discrepant between the two assays: one strongly positive (89% release) and six weakly positive samples by SRA (average release 56%) were WBIA negative. When these samples were retested using a random donor, only two remained SRA positive. Three samples were strongly WBIA positive but SRA negative; two were retested by SRA with 0.5IU/ml heparin and one became positive. Under controlled conditions, using the same selected high-responder donor, WBIA and SRA performed similarly with slightly increased sensitivity of the WBIA when using the strict definition of SRA positivity. WBIA is easy to perform with rapid turn-around time and warrants a multi-laboratory trial to complete its validation as a confirmatory assay for platelet-activating HIT antibodies.
肝素诱导的血小板减少症（HIT）仍然是一个挑战，只有通过功能检测才能确诊。金标准 14C- 血清素释放检测（SRA）具有很高的敏感性，但技术上具有挑战性，不适合常规使用。我们进行了一项大型研究，以验证全血阻抗聚集检测（WBIA）作为 HIT 的一种合适的诊断工具。WBIA 和 SRA 用于检测通过 PaGIA 或 ELISA 检测到 H-PF4 抗体阳性的 181 个样本。使用相同的高反应性供体，77 个样本通过 WBIA 呈阳性（低剂量而非高剂量肝素引起聚集）。使用 SRA 阳性的严格定义，72 个样本为真正的 HIT。在 9 个样本中，高剂量肝素引起的血清素释放下降超过 50%，但仍超过 20%；这些样本经半稀释后重新检测，其中 8/9 呈阳性。在两种检测方法中，有 10 个样本存在差异：一种强阳性（释放 89%）和 6 种弱阳性样本（SRA 平均释放 56%）WBIA 呈阴性。当使用随机供体重新检测这些样本时，只有 2 个样本仍为 SRA 阳性。3 个样本 WBIA 强阳性但 SRA 阴性；2 个样本用 SRA 以 0.5IU/ml 肝素重新检测，其中 1 个样本呈阳性。在受控条件下，使用相同的选定高反应性供体，WBIA 和 SRA 的性能相似，使用 SRA 阳性的严格定义时，WBIA 的敏感性略有提高。WBIA 易于操作，具有快速周转时间，值得进行多实验室试验，以完成其作为血小板激活型 HIT 抗体确认检测的验证。
